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Williams RM , Flesken-Nikitin A , Ellenson LH , Connolly DC , Hamilton TC , Nikitin AY , Zipfel WR
Strategies for High-Resolution Imaging of Epithelial Ovarian Cancer by Laparoscopic Nonlinear Microscopy
Translational Oncology. 2010 Jun;3(3) :181-194
PMID: ISI:000278913100006    PMCID: PMCID: PMC2887648   
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Ovarian cancer remains the most frequently lethal of the gynecologic cancers owing to the late detection of this disease. Here, by using human specimens and three mouse models of ovarian cancer, we tested the feasibility of nonlinear imaging approaches, the multiphoton microscopy (MPM) and second harmonic generation (SHG) to serve as complementary tools for ovarian cancer diagnosis. We demonstrate that MPM/SHG of intrinsic tissue emissions allows visualization of unfixed, unsectioned, and unstained tissues at a resolution comparable to that of routinely processed histologic sections. In addition to permitting discrimination between normal and neoplastic tissues according to pathological criteria, the method facilitates morphometric assessment of specimens and detection of very early cellular changes in the ovarian surface epithelium. A red shift in cellular intrinsic fluorescence and collagen structural alterations have been identified as additional cancer-associated changes that are indiscernible by conventional pathologic techniques. Importantly, the feasibility of in vivo laparoscopic MPM/SHG is demonstrated by using a "stick" objective lens. Intravital detection of neoplastic lesions has been further facilitated by low-magnification identification of an indicator for cathepsin activity followed by MPM laparoscopic imaging. Taken together, these results demonstrate that MPM may be translatable to clinical settings as an endoscopic approach suitable for high-resolution optical biopsies as well as a pathology tool for rapid initial assessment of ovarian cancer samples.
Williams, Rebecca M. Flesken-Nikitin, Andrea Ellenson, Lora Hedrick Connolly, Denise C. Hamilton, Thomas C. Nikitin, Alexander Yu. Zipfel, Warren R. National Institutes of Health [CA112354, CA96823, RR17595, CA116583, P41-RR04224, P50 CA083638] This work was supported by National Institutes of Health grants CA112354, CA96823, and RR17595 (to A.Y.N.); CA116583 and P41-RR04224 (to R.M.W. and W.R.Z.); and P50 CA083638 (to D.C.C., T.C.H., and A.Y.N.). 81 Neoplasia press; 1150 w medical center dr, msrb iii, rm 9303, ann arbor, mi 48109-0648 612pn